We tested the in vitro inhibitory activity of three 2',3'-dideoxynucleosides (ddN) and two viral binding inhibitors in combinations against the infectivity and cytopathic effect of human immunodeficiency virus type 1 (HIV-1). We found that either 3'-azido-2',3'-dideoxythymidine (AZT), 2'3'-dideoxyinosine (ddl), or 2',3'-dideoxycytidine (ddC) combined with soluble recombinant CD4 (sCD4) brings about a synergistic antiretroviral activity without toxicity at clinically achievable concentrations. Combinations of ddNs plus dextran sulfate also exerted similar synergistic antiviral effects without concomitant increases in toxicities. When sCD4 and dextran sulfate were combined, an apparent antagonism was observed. We confirmed that none of the combinations of sCD4 plus AZT, ddl, or ddC exerted significant increase in inhibitory effect on colony formation of human myeloid/ monocytic bone marrow cells in vitro at concentrations used in this study. These data might have a clinical relevance to the treatment of patients with HIV infection.